MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma
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Hao Yang1,2,*, Wei Zheng1,*, Xiao Shuai1, Rui-Min Chang1, Lei Yu1, Feng Fang1, Lian-Yue Yang1,3
1Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
2Department of Geratic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
3Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
*These authors have contributed equally to this work
Lianyue Yang, e-mail: [email protected]
Keywords: hepatocellular carcinoma, miR-424, Akt3, E2F3, tumor growth
Received: February 27, 2015 Accepted: July 23, 2015 Published: August 03, 2015
By comparing the expression profiles of miRNAs in different subtypes of HCC, we identified miR-424 as a HCC related miRNA. We found that the expression of miR-424 was significantly decreased in HCC tissues and six liver cancer cell lines. Significantly, its expression levels were correlated with tumor size, multiple nodules, vein invasion, TNM stage and overall survival of HCC. We showed that up-regulated miR-424 suppressed HCC cell proliferation in vivo and in vitro. Multi-pathway reporter arrays suggested that miR-424 suppressed the pRb-E2F pathway. Consistently, Akt3 and E2F3 were identified as the targets of miR-424 as evidenced by that ectopic miR-424 expression suppressed Akt3 and E2F3 expressions. Silencing Akt3 and E2F3 by siRNA pheno-copied the effect of ectopic miR-424 on HCC growth. Whereas, overexpression of Akt3 and E2F3 attenuated the effect of miR-424 on HCC growth. Together, our data demonstrated a tumor suppressor role for miR-424 in HCC development and progression with therapeutic implications. The strong correlation of miR-424 expression with HCC patient survival suggests that miR-424 could be a valuable biomarker for HCC prognosis.
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